1. Field of the Invention
This invention relates to a dry test strip for measuring the concentration of an analyte in a biological fluid; more particularly, a test strip that calorimetrically measures the concentration of glucose in whole blood.
2. Description of the Related Art
Many visual test devices have been developed for measuring the concentration of certain analytes in biological fluids. These devices have, for example, measured glucose, cholesterol, proteins, ketones, phenylalanine, or enzymes in blood, urine, or saliva.
Among the devices that are in most widespread use today is the blood glucose monitor. In the U.S. alone, there are estimated to be about 16 million people with diabetes. In order to avoid serious medical problems, such as vision loss, circulatory problems, kidney failure, etc., many of these people monitor their blood glucose on a regular basis and then take the steps necessary to maintain their glucose concentration in an acceptable range.
Reagent strips that are used in these devices contain an indicator that turns a different shade and/or intensity of color, depending on the concentration of glucose in the blood sample that has been applied to the strip. Although some of these strips use reduction chemistries, more commonly they involve an oxidizable dye or dye couple. Some of the strips include an enzyme, such as glucose oxidase, which is capable of oxidizing glucose to gluconic acid and hydrogen peroxide. They also contain an oxidizable dye and a substance having peroxidative activity, which is capable of selectively catalyzing oxidation of the oxidizable dye in the presence of hydrogen peroxide.
U.S. Pat. No. 4,292,272, issued Sep. 29, 1981 to M. Kitajima et al., discloses a multilayer strip for analysis that comprises a light-transmitting support, a reagent layer and a spreading layer, laminated together and to the support. The spreading layer is hydrophilic and supplies a liquid sample applied on its surface at a substantially constant volume per unit area to the reagent layer.
U.S. Pat. No. 4,631,174, issued Dec. 23, 1986 to A. Kondo, discloses a multilayer chemical analysis member that includes, superposed and bonded together, a support, a reagent layer, a porous spreading layer, and a waterproof layer. The waterproof layer has a small opening for applying a drop of sample. The sample diffuses through the spreading layer and into the reagent layer, where a color develops, as discussed above. The purpose of the waterproof layer is to retard evaporation of the sample, which xe2x80x9cinvariablyxe2x80x9d spreads outward laterally in the spreading layer, beyond the opening in the waterproof layer. Thereby, the xe2x80x9cmajor portion of fragile spreading layer is protected by the waterproof layer.xe2x80x9d
U.S. Pat. No. 4,935,346, issued Jun. 19, 1990 to R. Phillips et al., discloses a meter, strip, and method for determining the glucose concentration in a sample of whole blood (see also U.S. Pat. No. 5,304,468). The method involves simply applying a sample of whole blood to a first (xe2x80x9csamplexe2x80x9d) surface of an inert porous matrix that is impregnated with a reagent. The sample migrates toward the opposite, xe2x80x9ctesting,xe2x80x9d surface, as the glucose interacts with the reagent to produce a light-absorbing reaction product. A reading of reflectance from the testing surface indicates the glucose concentration. Reflectance measurements are made at two separate wavelengths in order to eliminate interferences. A timing circuit is triggered by an initial decrease in reflectance caused by wetting of the testing surface by the sample having passed through the matrix.
U.S. Pat. No. 5,200,148, issued Apr. 6, 1993 to Y. Saito, discloses a chemical assay tape that includes a support layer and at least one porous spreading layer. A reagent layer (and, optionally, a filter layer) may be sandwiched between the spreading layer and the support or, alternatively, the reagent may be incorporated into the spreading layer. Grooves cut into the spreading layer prevent cracking when the tape is wound.
U.S. Pat. No. 5,215,712, issued Jun. 1, 1993 to T. Kawanishi et al., discloses an apparatus and method for determining ion concentration, specific gravity, or osmotic pressure of a solution. An apparatus of the invention may contain a support having an opening that is covered with a transparent film, which, together with a reagent layer, sandwiches a spreading layer. The support layer is also provided with a retaining part.
U.S. Pat. No. 5,296,192, issued Mar. 22, 1994 to P. Carroll et al., discloses a diagnostic test strip for whole blood that has two support layers, between which are a spreading screen, a separating layer (to remove red blood cells), and a reagent layer.
U.S. Pat. No. 5,310,525, issued May 10, 1994 to S. Churchouse et al., discloses a fluid detection device that includes an impervious container having a fluid entry aperture and contiguous reagent and spreading layers. The device detects an analyte in a fluid that enters the container and spreads within the spreading layer. The analyte then initiates a reaction in the reagent layer to generate a signal.
U.S. Pat. No. 5,709,837, issued on Jan. 20, 1998 to T. Mori et al., discloses a dry analytical element that includes a support, a reagent layer on the support, and a porous spreading layer on the reagent layer. An adhesive layer may be on the regent layer to join the spreading layer.
U.S. Pat. No. 5,968,836, issued on Oct. 19, 1999 to D. Matzinger et al., discloses a reagent strip that has a testing pad sandwiched between a support and a transport medium. A fluid sample is applied to the transport medium and travels through it to the testing pad, in which a reagent reacts with an analyte of interest that is present in the sample to cause a color change. The support has an aperture, through which the color change in the testing pad can be viewed.
A meter that has come into widespread use for self-monitoring of blood glucose is the One Touch(copyright) Profile meter, which uses a strip that is described, inter alia, in U.S. Pat. Nos. 4,935,346 and 5,304,468, discussed above. The meter and strip permit a user to measure glucose concentration in a whole blood sample quickly, easily, and accurately. The sample is applied to one surface of the strip and the measurement made on the opposite surface. A portion of the whole blood sample penetrates from the sample surface to the testing surface, and the blood color can be observed from the testing surface.
The present invention provides a reagent test strip for use in an apparatus for determining an analyte concentration in a sample of biological fluid. The apparatus comprises optical means for detecting intensity of light reflected from a surface of the strip. The strip comprises
(a) a support having a through hole for passing a sample of the biological fluid,
(b) a mesh, having a first surface adjoining, and covering the hole in, the support, and
(c) a reagent matrix adjoining a second surface of the mesh, opposite the first surface, the matrix comprising
(i) a sample receiving surface for receiving the sample from the mesh and passing at least a portion of the sample toward a testing surface opposite to the receiving surface and
(ii) a reagent for indicating the analyte concentration, by creating at the testing surface a change in reflectance that can be related to the analyte concentration.
One embodiment of a reagent test strip of this invention is used in an apparatus that comprises optical means for detecting intensity of light at wavelengths of about 635 nm and about 700 nm reflected from at least a portion of the testing surface of the strip. In that embodiment, the invention provides a reagent test strip that is suitable for use in a One Touch(copyright) Profile whole blood glucose meter (or similar One Touch meter). Since the strip includes a mesh, which spreads the sample laterally, before the sample enters the matrix, it permits a glucose determination to be made using a smaller whole blood sample than is needed for a strip that lacks the mesh.